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Transcript
Institute for
Animal Health
News
Jenner Vaccine Foundation
Issue 02 | May 2010
Highlights
H1N1 ...Lessons from a pandemic | FMD and essential global control
Livestock vaccines and the Millennium Development Goals
HIV-1 Achilles heel | Meningococcal Disease - vaccine development
1
stable vaccines at tropical
temperatures - a solution
in sight
Simple and cheap is how this innovative technology
has been described, and it could be the
solution to one of Africa’s major problems…
how do you keep vaccines stable in
environments with unreliable
transport arrangements and
without a guaranteed electricity
supply for refrigeration
purposes?
Researchers from the Grand Challenges in
Global Health at the University of Oxford and
Nova Bio-Pharma Technologies have developed
a simple way of heat-stabilizing vaccines by
mixing the vaccines with the sugars trehalose
and sucrose. The mixture is then left to dry out
slowly on a filter or a membrane. The water
evaporates and the vaccine mixture turns into a
syrup and then solidifies. The thin sugary film
that forms can preserve the active part of the
vaccine in a “suspended animation”….when the
membrane is flushed with water the vaccine
is rehydrated and applied to a patient using a
normal plastic syringe.
The process is general and could be used
for many types of vaccines and sensitive
biological agents.
Professor Adrian Hill, principal
investigator and Director of the Jenner
Institute in which the Grand Challenge in
Global Health project is based, adds: ‘The
World Health Organization’s immunization
program vaccinates nearly 80% of the children
rd
it
rs
ive
f
yo
fo
Ox
Un
BiOtECanada
launches Vaccine
Policy Paper series
born today against six killer diseases: polio,
diphtheria, tuberculosis, whooping cough,
measles and tetanus. One of the biggest costs
is maintaining what’s called the cold chain
– making sure vaccines are refrigerated all
the way from the manufacturer to the child,
whether they are in the Western world or
the remotest village in Africa. If most or all
of the vaccines could be stabilized at high
temperatures, it would not only remove cost,
more children would be vaccinated.’
To watch the interview on this
development, view the following URL
http://www.ox.ac.uk/media/news_
stories/2010/100218_1.html.
This breakthrough technology has
been published in Science Translational
Medicine, Sci Transl Med 17 February 2010
2:19ra12.
For all enquiries contact Dr Matt Cottingham,
E [email protected]
T +44 (0)1865 617626
University of Oxford
Matt Cottingham
2
In Canada, as in the U.K., technology innovation
continues to drive the discovery of leading-edge
vaccines that will help transform the future of
public health worldwide. Recently, the Vaccine
Industry Committee of BIOTECanada (the
national non-profit association dedicated to
building Canada’s bio-economy) has launched
a 10-part series of policy papers that examines
the current system for introducing vaccines
in Canada – with a view towards promoting
vaccine R&D and improving timely access to
life-saving, cost-effective vaccine technologies
to protect individuals and societies, both in
Canada and abroad.
This comprehensive series, entitled,
“Building on the Legacy of Vaccines in Canada:
Value, Opportunities, and Challenges” (available
at www.biotech.ca/vaccines), provides a
unique, first-of-its-kind analysis of Canada’s
vaccine environment, underscoring the
tremendous medical, social and economic
value of vaccines. It also presents an in-depth
discussion of the opportunities and challenges
across the entire vaccine development chain,
from early-stage and clinical research, through
to vaccine licensure, establishing national
recommendations, identifying sustainable
funding mechanisms, and creating an enabling
infrastructure for vaccine manufacturing,
education, surveillance, and immunization
program implementation.
Each of the 10 policy papers provides
recommendations for government officials
and other key stakeholders, i.e. to help Canada
maintain its leadership position in the context
of global public health systems – and to
encourage the adoption of international best
practices for vaccine program development.
The series also represents a broad-based
educational resource for all immunization
stakeholders, with the goal of fostering critical
partnerships across vaccine researchers,
manufacturers, investment/funding
organizations, government agencies and
national advisory bodies, public health officials,
health professionals, public and private payers,
and the general public.
Enquiries may be directed to the author:
Dr. Nora Cutcliffe, Toronto, [email protected]
(Balliol College Alumnus, University of Oxford).
Update on H1N1 … lessons in responding
to a pandemic
Andrew J Pollard,
Professor of Paediatric Infection & Immunity
Director of the Oxford Vaccine Group,
University of Oxford
In the future we may be able to fully predict
the risk posed by novel influenza viruses
from their genetic code but this is not the
case yet, and decisions on the national and
international responses to the threat must
be made with this limited vision.
Because the pandemic claimed fewer
lives than it might have, the policy makers
have been heavily criticised for overuse of the
drug oseltamivir to treat suspected cases and
Anna Tanczos/Wellcome Images
While the H1N1 influenza pandemic of 2009 was
very real with rapid spread around the world of
this novel strain, and well documented and highly
publicised serious disease and deaths in children,
younger adults and pregnant women, the
numbers of severe cases were far lower than
seen in previous pandemics. Older adults, who
suffer a high burden of influenza morbidity
from seasonal flu, were relatively unaffected by
this virus as a result of pre-existing immunity
acquired from flu viruses that circulated in the
1950s.The active global influenza surveillance
network and rapid access to genetic information
identifying the H1N1 swine flu virus as novel,
allowed the World Health Organisation to recognise
its pandemic potential earlier than in any previous
pandemic, and before there was extensive
epidemiological data available.
wasting money on purchase of excessive
numbers of doses of vaccines to prevent the
disease that were not used.
While some of the policy decisions
made as the pandemic evolved can be
criticised (oseltamivir policy being a
good example), I see no conspiracy here.
The authorities predictions turned out to
be wrong, but we only really know that
with hindsight and it might have been
so different. If the death rate had been
higher and our hospitals over-flowing
with critically ill patients, the extensive
preparations and cost would have been
fully justified (and likely the authorities
would have been criticised for not going
further!). However, because we escaped
devastation this time, the greatest risk to
our safety with the next pandemic threat
may well be the hesitation of bruised
governments and international authorities
who fear calling it too soon.
This pandemic has driven new
knowledge in the influenza field and our
experiences with new vaccines could lead
to improvements in influenza prevention in
the future, both for pandemic and seasonal
flu. Influenza is a serious disease which
claims vulnerable lives across the age range
and burdens our health care systems every
year, even in the absence of a pandemic,
so it is right to continue to take this virus
seriously.
3
Connecting the dots; clearing
a pathway from livestock
vaccines to Millennium
Development Goals
Brian Perry,
Visiting Professor of Tropical Veterinary Medicine
Nuffield Department of Clinical Medicine, University of Oxford, UK
and Honorary Professor, College of Medicine and Veterinary Medicine,
University of Edinburgh, UK and Honorary Professor,
Department of Veterinary Tropical Diseases, University of Pretoria, South Africa
As an epidemiologist in the
development arena I am regularly
asked to substantiate the connection
between technological innovations,
such as vaccines, and measurable
outcomes of benefit to global society,
such as the Millennium Development
Goals (MDGs). Metrics of potential
impact are increasingly demanded by
many research investors, who need
evidence of demonstrable returns.
MDG 1 aims to halve the proportion of
people whose income is less than US$
1 per day, and the proportion of people
who suffer from hunger, by 2015.
In considering returns to livestock vaccines, our
baseline is that three quarters of the world’s poor
live in rural areas, in Africa 65% of rural income
comes from farming, and livestock contribute
some 30% of agricultural GDP in developing
countries.Livestock are an expression of poverty
for most, a bank account for some, and an
opportunity to escape from poverty for a few;
how will vaccines bring change, and which ones
should we focus on?
I led a conceptualisation of livestock’s
contributions to processes of poverty reduction,
developed to illustrate how different animal
diseases and their control affect the poor;
it presented a troika of livestock-mediated
“pathways to poverty reduction”. These are:
reducing vulnerability, improving productivity
performance, and improving market access.
Different diseases affect these pathways
in different ways. Epidemic and zoonotic
diseases (Newcastle disease, rinderpest, Rift
Valley fever) destroy fundamental assets
and increase vulnerability; vector-borne and
parasitic diseases disturb performance; and
transboundary (foot-and-mouth disease and
African swine fever) and zoonotic (cysticercosis)
diseases disrupt or prevent market access. The
conceptualisation also produced a ranking of
The Ethiopian, British and French team engaged in rinderpest
vaccination on the southern border with Kenya in 1972
Brian Perry flying rinderpest vaccine in to his teams in 1972
4
Cattle threshing the teff harvest in Ethiopia
disease importance, based on expert opinion of
the impacts of the diseases on the poor, overlaid
with the calculated density of poor people. A
crude approach, perhaps, but a first cut. What
this did not do was to calculate the returns
to reducing the incidence of these diseases
through vaccines and other interventions, and
use the differential benefits as the basis for
priority setting; given the inadequacies of data,
this gap remains largely unfilled.
Perhaps the best model of vaccine’s
contribution to the MDGs is that of rinderpest;
we are shortly to hear that this ancient disease
has been eradicated. An effective vaccine
(pioneered by the late Walter Plowright, a
former department head at IAH) combined
with a well-funded, coordinated global
programme have yielded extraordinary
results. The disappearance of rinderpest has
undoubtedly removed a significant threat to
the vulnerability of poor livestock keepers,
particularly in the pastoralist systems of Africa.
The irony is that we have still not been able to
measure effectively the impacts of rinderpest
eradication, nor synthesise objectively the
reasons for this formidable success. The
decision in 1960 to embark on a pan-African
eradication programme was made without
an ex ante economic impact assessment,
before most African countries had gained
independence, and long before the mindset
of poverty reduction and MDGs had hit the
disease control investment world. While
vaccines are almost universally recognised as
the most effective tools to prevent infectious
diseases, the justification for livestock vaccine
research, and certainly for embarking on
disease eradication, now demands a more
quantitative and comparative understanding
of the future benefits to be reaped by different
stakeholders engaged in livestock enterprises
and value chains, if it is to attract the sort of
investment and political commitment required
to achieve the ultimate prize of eradication.
Attacking the
Achilles heel of HIV-1
Dealing with HIV-1 diversity
Lucy Dorrell and Tomáš Hanke, Jenner Investigators,
Weatherall Institute of Molecular Medicine,
University of Oxford
Development of an effective, accessible vaccine is the best
hope for halting the HIV-1 epidemic. As discussed in the
previous newsletter, most researchers believe that a vaccine
should induce effective B cell responses and T cell responses
at the same time. Nature does not provide an example
of a protective immune response since no-one has ever
been confirmed to have successfully cleared HIV-1 infection.
Therefore, both of these goals present substantial challenges
which need to be overcome separately before combining two
successful solutions into a single vaccine strategy.
We have focused on developing vaccines
which aim to promote T cell responses.
Because of the extensive genetic variation in
circulating HIV-1 strains, T cell responses
must be effective against diverse viral
variants circulating in the target population
and against viral escape mutants arising in
individuals who fail to prevent the infection.
We hypothesized that HIV-1 variation would
be best tackled by targeting functionally
conserved regions of the virus. Thus, we
assembled from the 14 most invariable
segments of the HIV-1 proteome into a
single chimeric protein called HIVconsv.
Each segment is 27-128 amino acids
in length and is derived from the four
major HIV-1 clades A, B, C and D
alternating to ensure that they are equally
represented. Clade consensus (or average)
sequences are used to ensure coverage of
the variability within
individual clades.
We predict that the
functional conservation
of these regions
limits the chance of
mutations allowing
HIV-1 to escape the
vaccine-elicited T cell
responses and that any
mutations which would
arise will result in a
significantly reduced
viral fitness (capacity to
replicate). The HIVconsv
immunogen is expressed
from DNA plasmid
and two attenuated,
non-replicating viral
vectors: MVA used in
the past as a smallpox
vaccine and ChAdV-63,
a highly immunogenic
adenovirus of
chimpanzee origin,
which does not have a
pre-existing immunity
in humans that dampens
its efficacy as observed
in the STEP trial for its
human cousin HAdV-5.
A triple heterologous
vector regimen delivering HIVconsv elicits
stronger T cell responses than simpler
regimens, which have not been hugely
successful in human efficacy trials so far.
We aim to use the HIVconsv vaccines
both for treatment and prevention. For
vaccine inducing T cell responses this means
to provide a long-term drug-free control
of HIV-1 in patients who already have the
infection and in healthy, HIV-1-uninfected
individuals who are likely to be exposed
to HIV-1 in the future. For therapeutic
immunisation, we envisage using ChAdV-63
and MVA-vectored HIVconsv vaccines in
combination with a course of antiretroviral
drug treatment started in early infection.
For prevention, all three HIVconsv vaccines
will be combined in a heterologous regimen
using the plasmid DNA as a prime. In
future, when an effective B cell vaccine is
developed, our T cell-eliciting regimen could
be combined with the B cell approach into
a single formulation/regimen for maximum
benefit to vaccinees.
We began first-in-human testing of
MVA.HIVconsv as a therapeutic vaccine in
Oxford in January 2010. Twenty patients with
HIV-1 infection will receive MVA.HIVconsv
vaccinations in addition to antiretroviral
therapy. Later in 2010, we will begin phase
I testing of the triple vaccine combination
in 32 healthy, HIV-1-seronegative low-risk
volunteers.
5
FMD - not without its
challenges, but its global
control is essential for
international development
David Paton, Head, Foot-and-Mouth Disease Programme,
Institute for Animal Health
Foot-and-mouth disease is considered one of the biggest threats to livestock and
the losses that it causes are most severe amongst modern and highly productive
breeds of animal. It is caused by a small but highly contagious virus that affects
multiple domestic species including cattle, sheep, pigs and buffalo as well as a
range of wildlife. Its worldwide distribution closely mirrors economic prosperity;
most developed countries have eradicated FMD and most developing countries
lack the resources to do so. This imbalance impacts international trade because
FMD-free countries restrict imports of animals and their products if they originate
from infected countries. This has a knock-on effect in reducing investment in and
development of livestock industries in countries where such improvements are
most needed. Meanwhile, periodic incursions of the disease into previously FMDfree countries can cost billions of pounds, such as occurred in the UK in 2001.
Better control of FMD in endemically
affected countries will also benefit
countries that are disease-free but current
vaccines are less than ideal for achieving
this goal. Their most significant failings
are that they have to be given repeatedly
to sustain immune protection and that
they are very unstable in warm climates
making it difficult to get them to their
point of use without a well organised
and resourced system of refrigeration. In
addition, current vaccines are produced
from growing up and then inactivating
large quantities of live virulent FMD
virus, a procedure that is not without
risk of virus escape. One approach to
overcome these difficulties is to use
genetic engineering to produce viral shells
that retain the immunogenic components,
lack the infectious viral genome, but have
been altered to enhance their thermal
stability. This would be a safe way to
produce a vaccine that would not require
a cold chain. Meanwhile, the enhanced
stability might also lead directly to a more
long lasting immune response, as well
as providing options for new delivery
systems that could also prolong immune
memory.
All images: Institute for Animal Health
Cell (red) supporting the
replication of FMDV (green)
adjacent to the nucleus (blue)
6
3D structure of FMDV 1
3D structure of FMDV 2
3D structure of FMDV 3
3D structure of FMDV 4
One Health Initiative
One Health is a world-wide initiative that
supports improvement in the lives of both species
- human and animal - through the increased
and enhanced integration of human and animal
medicine. The Jenner Vaccine Foundation
newsletter is now featured in the Publications
section of the One Health Initiative website
been appointed, one working with the Bovine
TB group at Compton lead by Jayne Hope and
the Oxford human TB vaccine programme
lead by Helen McShane, and the other linking
the activities of the human influenza vaccine
programme (Sarah Gilbert, Oxford) and avian flu
vaccine development ( Colin Butter, Compton).
http://www.onehealthinitiative.com/index.php.
The Foundation looks forward to working closer
with the One Health Initiative and bringing
news and developments to the attention of our
readership.
The two Jenner Fellow appointments
advertised in the previous Newsletter have
IAH
IAH
Andrew J Pollard,
Professor of Paediatric Infection & Immunity
Director of the Oxford Vaccine Group,
University of Oxford
Meningitis B (the group B meningococcus)
is the leading cause of bacterial meningitis
and septicaemia in the UK causing up to
1500 cases each year and is the leading cause
of death in childhood by infectious agents.
Meningitis is a disease affecting the
protective membrane covering the brain
and spinal fluid. The membrane becomes
inflamed following infection by bacteria,
of which the most common in the UK are
group B and group C meningococci. Vaccine
development is a public health priority
and the development and introduction of a
vaccine in 1999 for Group C meningococcus
has already successfully reduced the
incidence in the targeted age groups by over
90%.1
However, the development of a vaccine
for Group B is a far bigger challenge. The
successful meningitis vaccines developed to
date have been based on the sugar coat of
the bacteria, but, with meningococcus B, the
surface of the organism is cloaked in sugars
which are identical to polysaccharides
found on some human cells and therefore
are not recognised by our immune system.
Development of a vaccine has been
hampered even further by the variability of
many of the surface proteins beneath the
sugar coat.
Professor Andrew Pollard and
Professor Martin Maiden, both at the
Jenner Institute, with Professor Jeremy
Derrick (Manchester University) and
Professor Ian Feavers (National Institute
for Biological Standards and Control) have
been awarded a Wellcome Trust Strategic
Translation Award, building on a previous
Wellcome Trust vaccine development grant,
to develop a promising meningococcal
B vaccine candidate that could prevent
thousands of cases.
The unique potential of the vaccine
has arisen from important observations
showing that a limited repertoire of the
variable surface proteins are associated
with the bacteria that cause the disease in
humans. The vaccine is therefore composed
of a combination of these proteins known
Provided courtesy of Professor David Ferguson and Dr Martin Callaghan
Development of a Protein (PorA/FetA) vaccine to prevent
meningococcal disease - Group B meningitis.
as PorA (porin), and FetA (iron-regulated
surface protein). The prototype vaccine is
currently being manufactured for testing in
humans in 2011.
Immunogold electron micrograph of a meningococcus,
showing binding of antibodies in murine sera following
immunisation of mice with recombinant Opa protein
(black dots). These antibodies resulted in bacterial killing,
providing proof in principle that Opa proteins could be a
novel serogroup B meningococcal vaccine candidate.
1 http://www.meningitis.org/disease-info/vaccines
7
Grant Start-Up Meeting in Dakar, Senegal, February 2010
Attendees from Oxford, Senegal, South Africa and The Gambia at the MVA85A Grant Start-up Meeting in Dakar, Senegal, February 2010
New tB Vaccine in Multiple Phase iib trials in Africa
The new TB vaccine, MVA85A, was developed by Dr Helen McShane (a Jenner
Investigator) and has already undergone successful testing in Phase I and
IIa trials in the UK and Africa. MVA85A is designed to enhance the immune
response to the currently used TB vaccine, BCG, which although protective
in infants, does not work well in adults or against lung disease.
As reported in the previous Jenner
newsletter, MVA85A is now being
evaluated in a Phase IIb efficacy trial in
South African infants. Of the total 2800
infants in this study, over 800 have so far
been enrolled with recruitment proceeding
well.
Now, a second Phase IIb efficacy trial
with MVA85A is about to commence
in HIV-infected adults. The trial, which is
planned to start later this year, will recruit
~1400 HIV-infected subjects from two
different sites – one in Cape Town, South
Africa and one in Dakar, Senegal. Previous
Phase IIa trials have shown that the vaccine
is safe in this population and stimulates a
good immune response, but this is the first
time that MVA85A will be tested to see if it
prevents TB disease in this population. The
trial will run over about four years and, like
the infant trial, half the subjects will receive
MVA85A and half will receive a placebo.
Funding for the trial comes,
predominantly, from the European and
Developing Countries Clinical Trials
Partnership (EDCTP). This trial will be
run in conjunction with the University
of Cape Town, Le Dantec University in
Dakar, the MRC unit in The Gambia, the
Institute for Public Health in Brussels, the
Oxford-Emergent Tuberculosis Consortium
(OETC) and the Aeras Global TB Vaccine
Foundation, who are also the trial sponsor
and are providing additional funding.
license agreement news ...
Biopharmaceutical company Imaxio has
announced that it has entered a reciprocal
license agreement with Isis Innovation, the
technology transfer arm of Oxford University, to
exploit know-how arising out of joint research at
one of the world’s premier research institutions,
the Jenner Institute, for the development
of new vaccines. The agreement will allow
Imaxio to use its proprietary aXent adjuvant
technology with viral vectors such as Modified
Vaccinia Ankara (MVA) and adenoviruses.
The University of Oxford is internationally
recognised for its expertise in the creation and
development of virally vectored vaccines.
8
“The technology Isis has licensed to us
further validates the ability of Imaxio’s aXent™
technology to enhance immune responses to
current and future vaccines, and particularly
those using viral vectors,” said Francois Miceli,
Chief Executive Officer of IMAXIO. “Oxford
and the Jenner Institute have been excellent
sources of innovation in the vaccine field.”
Oxford also benefits, as it secures the
right to use the Imaxio adjuvant in developing
its own vaccines candidates, which would
then be made available for partnering and
further development through Isis. The current
agreement is the result of a collaboration which
started in 2004 and has already led to joint
patent filings. This collaboration is financed in
part by the Grand Challenges in Global Health
consortium, a programme supported by the
Gates Foundation to promote innovation in
global health.
Profiling: Jenner Investigators
Lucy Dorrell
I received my Bachelor of Medicine degree
from the University of Southampton in 1988
and began my research career in 1993 as a
Clinical Research Fellow in Communicable
Diseases and Genitourinary Medicine at
Imperial College. Initially, I was involved in
clinical trials of new antiretroviral drugs; there
was no effective treatment for HIV infection at
this time. My interest in immunology began
with research into antigen-presenting cell
function in HIV infection, leading to an DM
degree (1998). I moved to Oxford University
in 1997 to study immunity to HIV-1/HIV-2 in
exposed-infected individuals with Professors
Sarah Rowland-Jones and Hilton Whittle,
spending two years at MRC Laboratories,
The Gambia. After completing specialist
clinical training (Genitourinary / HIV Medicine),
I returned to the lab as a Clinician Scientist
Fellow and began investigating the potential
to augment protective CD8+ T cell responses
against HIV-1 by therapeutic vaccination
using novel DNA and viral-vectored HIV-1
vaccines developed by Dr Tomáš Hanke and
Professor Andrew McMichael (MRC Human
Immunology Unit, Weatherall Institute of
Molecular Medicine). I became a Senior
Clinical Lecturer in 2007 and continue to work
on immunomodulation in HIV-1 infection
within the Immunity theme of the Oxford
NIHR Biomedical Research Centre. Currently,
we are testing a new approach to tackling
HIV-1 variability and immune escape using
heterologous prime-boost vaccinations
with a novel immunogen based on highly
conserved regions of the HIV-1 genome.
Another obstacle to the development of an
effective HIV-1 vaccine candidate is the lack
of a correlate of protective immunity. We
are investigating novel immune correlates,
including the antiviral inhibitory capacity of
HIV-specific CD8+ T cells, which may provide
a better measure of a protective immune
response than widely used cytokine-based
assays, and thus could be used to predict
vaccine efficacy in early trials.
Key Publications
years working in veterinary practice in UK
and Australia, I have spent the last 23 years
as a veterinary virologist specialising in
the epidemiology, diagnosis and control
of various viral livestock diseases. I joined
the Virology Department of the Central
Veterinary Laboratory (later Veterinary
Laboratories Agency, VLA). I was for six
years secretary of the European Society
for Veterinary Virology and became
head of the Virology department at VLA
in 1998. In 2001, I left VLA to join the
Institute for Animal Health (IAH) as head
of the department for vesicular disease
control that includes the FAO foot-andmouth disease (FMD) world reference
laboratory. In 2007, I became head of the
FMD Programme at IAH with 45 scientists
plus students. The work of the Programme
includes a wide range of strategic and
applied research on FMD control including
the evaluation of vaccination strategies
as well as the development of improved
vaccines and vaccine selection methods.
Key Publications
Yang H, Guimarães-Walker A, Hibbs S, Dong T, Stacey A,
Borrow P, Hanke T, Davenport MP, McMichael A, Dorrell L.
Interleukin-10 responses to therapeutic vaccination during
highly active antiretroviral therapy and after analytical therapy
interruption. AIDS. 2009 Oct 23;23(16):2226-30.
Murphy RL, Autran B, Katlama C, Brucker G, Debre P, Calvez V,
Clotet B, Clumeck N, Costagliola D, Deeks SG, Dorrell L, Gatell J,
Haase A, Klein M, Lazzarin A, McMichael AJ, Papagno L,
Schacker TW, Wain-Hobson S, Walker BD, Youle M.
A step ahead on the HIV collaboratory. Science. 2009;
324(5932):1264-5.
Yang H, Dong T, Turnbull E, Ranasinghe S, Ondondo B,
Goonetilleke N, Winstone N, di Gleria K, Conlon C, Borrow P,
Hanke T, McMichael A & Dorrell L. Broad TCR usage in
functional HIV-1-specific CD8+ T cell expansions driven
by vaccination during highly active antiretroviral therapy. J
Immunol. 2007;179:597-606.
Ondondo B, Yang H, Dong T, de Gleria K, Goonetilleke N,
Winstone N, Conlon C, Rowland-Jones S, Hanke T, McMichael
A & Dorrell L. Immunisation with recombinant modified
vaccinia virus Ankara expressing HIV-1 gag in HIV-1-infected
subjects stimulates broad functional CD4+ T cell responses. Eur
J Immunol. 2006 ;36:2585-94.
Dorrell L, Yang H, Ondondo B, Dong T, di Gleria K, Suttill A,
Conlon C, Brown D, Williams P, Bowness P, Goonetilleke N,
Rostron T, Rowland-Jones S, Hanke T & McMichael A.
Expansion and diversification of virus-specific T cells
following immunisation of HIV-1-infected individuals with
a recombinant modified vaccinia virus Ankara / HIV-1 gag
vaccine. J Virol 2006; 80: 4705-4716.
David Paton
I obtained my BA (Hons) Natural Sciences
and VetMB degrees from the University
of Cambridge, UK in 1981 and 1984
respectively, and a PhD degree, from the
University of Surrey, UK, in 1992. After three
Parida S, Fleming L, Oh Y, Mahapatra M, Hamblin P, Gloster J, Paton
DJ. (2008). Emergency vaccination of sheep against foot-and-mouth
disease: significance and detection of subsequent sub-clinical
infection. Vaccine 26(27-28): 3469-79.
Cottam EM, Wadsworth J, Shaw AE, Rowlands RJ, Goatley L,
Maan S, Maan NS, Mertens PPC, Ebert K, Li Y, Ryan ED, Juleff N, Ferris
NP, Wilesmith JW, Haydon DT, King DP, Paton DJ, Knowles NJ. (2008).
Transmission pathways of foot-and-mouth disease virus in the United
Kingdom in 2007. PLoS Pathogens 4, 1-8.
Arnold ME, Paton DJ, Ryan E, Cox SJ, Wilesmith JW. (2008). Modelling
studies to estimate the prevalence of foot-and-mouth disease carriers
after reactive vaccination. Proc Biol Sci.275(1630):107-15.
Paton DJ, Sumption KJ, Charleston B. (2009). Options for control
of foot-and-mouth disease: knowledge, capability and policy.
Phil Trans R Soc B 364, 2657-2667.
Valarcher J-F, Knowles NJ, Zakharov V, Sherbakov A, Zhang Z, Shang
Y-J, Liu Z-X,Liu X-T, Sanyal A, Hemadri D, Tosh C, Rasool TJ, Pattnaik B,
Schumann K, Beckham TR, Linchongsubongkoch W, Ferris NP, Roeder
PL, Paton DJ. (2009). Multiple origins of a foot-and-mouth disease virus
serotype Asia 1 epidemic. Emerging Infectious Diseases, 15(7):1046-51.
Fowler VL, Knowles NJ, Paton DJ, Barnett PV. (2010). Marker vaccine
potential of a foot-and-mouth disease virus with a partial VP1 G-H
loop deletion. Vaccine 28, 3428-3434.
9
Jenner Investigator Profiles continued
Andrew Pollard
I am Professor of Paediatric Infection and
Immunity at the University of Oxford,
Director of the Oxford Vaccine Group in the
University Department of Paediatrics, Fellow
of St Cross College and Honorary Consultant
Paediatrician at the Children’s Hospital, Oxford,
UK. I chair the UK’s NICE meningitis guidelines
development committee. I obtained my
medical degree at St Bartholomew’s Hospital
Medical School, University of London in 1989
and trained in Paediatrics at Birmingham
Children’s Hospital, UK, specialising in
Paediatric Infectious Diseases at St Mary’s
Hospital, London, UK and at British Columbia
Children’s Hospital, Vancouver, Canada.
I obtained my PhD at St Mary’s Hospital,
London, UK in 1999 studying immunity
to Neisseria meningitidis in children and
proceeded to work on anti-bacterial innate
immune responses in children in Canada
before returning to my current position at
the University of Oxford, UK in 2001. Current
research activities include clinical trials of
new and improved vaccines for children,
invasive bacterial diseases in children in Nepal,
studies of cellular and humoral immune
responses to glycoconjugate vaccines,
research on the genetic control of the human
immune response and investigations on
meningococcal host-pathogen interactions
and development of a serogroup B
meningococcal vaccine. My publications
include over 200 manuscripts and books on
various topics in paediatrics, and infectious
diseases.
Key Publications
I started my undergraduate studies
at Charles University in Prague,
Czechoslovakia reading Chemistry and
completed my B.Sc. Honours degree in
Biochemistry at McMaster University in
Hamilton, Canada, where I also received
an M.Sc. for my studies on Herpes simplex
virus immunology. I then moved to St.
Andrews University in Scotland for my Ph.D.
degree developing antiviral-vaccines as
solid matrix-antibody-antigen complexes.
In 1994, I arrived as a post-doctoral scientist
in Professor McMichael’s laboratory in the
Weatherall Institute of Molecular Medicine
in Oxford, where I started working on the
development of HIV vaccines, my current
interest. With the establishment of the MRC
Human Immunology Unit in 1998, I started
my own group and 5 years later, I obtained
my MRC tenure position. Since 2007 and
2008, I have been a Jenner Investigator and
Reader in Immunology, respectively.
Key Publications
Snape MD, Perrett KP, Ford KJ, John TM, Pace D, Yu
L, Langley JM, McNeil S, Dull P, Ceddia F, Anemona
A, Halperin SA, Dobson S, Pollard AJ. A randomized
controlled trial of a novel tetravalent meningococcal
glycoconjugate vaccine in infants. JAMA 2008 Jan
9;299(2):173-84.
Lee YC, Kelly DF, Yu LM, Slack MP, Booy R, Heath PT,
Siegrist C-A, Moxon ER, Pollard AJ. Haemophilus
influenzae type b vaccine failure in children is associated
with inadequate production of high quality antibody.
Clinical Infectious Disease, 2008 Jan 15;46(2):186-92.
Snape MD, Kelly DF, Lewis S, Banner C, Kibwana L,
Moore C, Diggle L, John T, Yu LM, Borrow R, Borkowski
A, Nau C, Pollard AJ. Sero-protection against serogroup
C meningococcal disease in adolescents in the United
Kingdom: an observational study.
BMJ 2008 Jun 28;336(7659):1487-91. Epub 2008 Jun 5.
Kelly DF, Snape MD, Clutterbuck EC, Green S, Snowden C,
Diggle L, Yu LM, Borkowski A, Moxon ER and Pollard AJ.
CRM197-conjugated serogroup C meningococcal
capsular polysaccharide, but not the native
polysaccharide, induces persistent antigen-specific
memory B cells. Blood 2006;108(8):2642-7.
Pollard AJ, Perrett KP, Beverley PC. Maintaining protection
against invasive bacteria in childhood with protein–
polysaccharide conjugate vaccines. Nature Reviews of
Immunology 2009 Mar;9(3):213-20.
Tomáš Hanke
Rosario M, Hopkins R, Borthwick N, Fulkerson J, Quigley MF,
Hill BJ, Joseph J, Douek DC, Price DA, Both GW, Sadoff JC and
Hanke T. Novel recombinant BCG, ovine atadenovirus and
modified vaccinia virus Ankara vaccines combine to induce robust
polyfunctional human immunodeficiency virus-specific CD4 and
CD8 T cell responses in rhesus macaques. J Virol In press (2010).
Bridgeman A, Roshorm Y, Lockett LJ, Xu Z-Z, Hopkins R,
Shaw J, Both GW and Hanke T. Ovine Atadenovirus, a novel highly
immunogenic vector for candidate HIV-1 vaccines. Vaccine
28:474-483 (2009).
Roshorm Y, Hong JP, Kobayashi N, McMichael AJ, Volsky AJ,
Potash MJ, Takiguchi M and Hanke T. Protection of mice against
chimaeric human immunodeficiency virus type 1 challenge by
clade B vaccine designed for HLA-B*5101+ patients.
Eur J Immunol 39:1831-1840 (2009).
Létourneau S, Im E-J, Mashishi T, Brereton C, Bridgeman A,
Yang H, Dorrell L, Dong T, Korber B, McMichael AJ and Hanke T.
Design and pre-clinical evaluation of a universal HIV-1 vaccine.
PLoS ONE 2:e984 (2007).
Im E-J, Saubi N, Virgili G, Sander C, Teoh D, McShane H, Joseph J
and Hanke T. Vaccine platform for prevention of tuberculosis and
mother-to-child transmission of HIV-1 through breastfeeding.
J Virol 81:9408-9418 (2007).
Hanke T, and McMichael AJ. Design and construction of an
experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.
Nat Med 6, 951-955 (2000).
10
Brian Perry
I graduated as a vet from the University of
Edinburgh in 1969, and after a brief spell in
mixed animal practice took the Diploma in
Tropical Veterinary Medicine, also in Edinburgh.
This set me up to join the rinderpest eradication
programme, working for the Imperial Ethiopian
government and supported by the UK Overseas
Development Administration (now DFID). I then
returned to the UK to take a MSc in tropical
veterinary science (again in Edinburgh), before
moving to Colombia to run an investigation
laboratory specialising in sheep diseases. Three
years later I was next taken on by the Food and
Agriculture Organisation of the United Nations
(FAO) as epidemiologist in Zambia, studying
the dynamics and impacts of livestock diseases
affecting the smallholder farming sector. The
next leap was to Virginia, USA, where I was
recruited as the epidemiologist in the newly
established Virginia-Maryland Regional College
of Veterinary Medicine, where as an Associate
Professor I obtained tenure, and a Doctorate
(yet again from Edinburgh!). After almost two
decades of nomadic behaviour I returned
to Africa in 1987 to lead the newly created
Epidemiology and Socioeconomics Programme
at the International Laboratory for Research
on Animal Diseases (ILRAD) in Nairobi, Kenya.
In 1995 ILRAD became ILRI (the International
Livestock Research Institute), and broadened its
geographical mandate to regions outside Africa.
I left ILRI three years ago in 2007, but still live in
Kenya, now in the Rift Valley. Under the auspices
of the Jenner, I have led the development of
two large strategic research award proposals
on the understanding of endemic foot-andmouth disease (FMD), and have recently led
the independent team evaluating FAO’s global
programmes on avian influenza.
My specialisation has been in developing
country livestock systems and in veterinary
epidemiology, and I have applied the expanding
inventory of epi and impact assessment tools
in researching several different diseases such as
gastro-intestinal parasitism, rabies, theileriosis,
heartwater and FMD, mostly associated with
the improved use of vaccines in their control.
Frustrated at the slowness of change in disease
control in much of the developing world, I have
specialised in advocating the use of the products
of epidemiology and economics studies to
influence the development of sound evidencebased policies and strategies.
The innovative vaccine design programme seeks to
design and develop promising new vaccines against
infectious diseases of global health importance such
as pandemic influenza, malaria and meningitis,
using a broad multi-disciplinary set of approaches
ranging from structural biology, genomics and
mathematical modeling to immunology, clinical
trials and health economics.
Brian has published more than 250 scientific articles in
refereed journals, books and proceedings. Below is a brief
selection.
Perry, B.D. and Grace, D. (2009). The impacts of livestock
diseases and their control on growth and development
processes that are pro-poor. Philosophical Transactions of
the Royal Society, B, 364, 2643 - 2655.
Perry, B.D. and Sones, K.R. (Editors) (2007). Global
Roadmap for Improving the Tools to Control Foot-andMouth Disease in Endemic Settings. Report of a workshop
held at Agra, India, 29 November –1 December 2006, and
subsequent Roadmap outputs. ILRI (International Livestock
Research Institute), Nairobi, Kenya, 88 pp. and CD-ROM.
Perry, B.D. and Rich, K (2007). The poverty impacts of footand-mouth disease and the poverty reduction implications
of its control. Veterinary Record, 160, 238-241.
Perry, B.D., McDermott, J.J. and Randolph, T.F. (2001).
Can epidemiology and economics make a meaningful
contribution to national animal disease control? Preventive
Veterinary Medicine, 48, 231-260.
Coleman, P. G., Perry, B.D. & Woolhouse, M.E.G. (2001).
Endemic stability: a veterinary idea applied to human
public health. The Lancet. 357, 1284-1286.
Perry, B.D., McDermott, J.J. and Randolph, T.F. (2004).
Control of infectious diseases: making appropriate decisions
in different epidemiological and socio-economic conditions
In: Infectious Diseases of Livestock, Volume 1, Editors J.A.W.
Coetzer and R.C. Tustin, Oxford University Press, Cape Town,
178-224.
Perry, B.D., Randolph, T.F., McDermott, J.J., Sones, K.R. and
Thornton, P.K. (2002). Investing in Animal Health Research
to Alleviate Poverty. International Livestock Research
Institute (ILRI), Nairobi, Kenya, 140 pp plus CD-ROM.
O’Callaghan, C.J., Medley, G.F., Peter, T.F. and Perry, B.D.
(1998). Analysis of the epidemiology of heartwater
(Cowdria ruminantium infection) in a transmission
dynamics model. Parasitology. 117, 49-61.
Rob Judges
James Martin 21st Century
School $50m Challenge to benefit
innovative vaccine design, 1 of the
19 projects that were successful in
the matched funding scheme
Key Publications
Lead Researcher(s): Professor Adrian Hill,
Director of the Jenner Institute, and Professor
Susan Lea, Professor of Chemical Biology,
University of Oxford, meet with philanthropist
James Martin following the announcement
of their successful application
11
Take note....
A Discussion Meeting on “New
Vaccines for Global Health” is to be
held at the Royal Society, London,
on 15- 16 November 2010. Many new
vaccine technologies are becoming
available to address global health
priorities. This 2-day meeting will
review vaccine design, development
and deployment, in the search for
vaccines against major killers such as
malaria, HIV/AIDS and tuberculosis.
Wellcome Grant Award
The Wellcome Trust has awarded £1.3M to the IAH and collaborators to
investigate the translation of fundamental research into novel ways
of producing better foot-and-mouth disease virus (FMDV) vaccines at a
commercial level. The collaboration partnership will be led by Dr Bryan
Charleston of IAH, and will involve the Department of Structural Biology
(University of Oxford), Intervet-Schering Plough Animal Health (IntervetSPAH, Netherlands), ARC-Onderstepoort Veterinary Institute (South Africa),
the Agricultural Research Service (USA), and the USDA - Foreign Animal
Disease Research Unit at Plum Island (USA)
Organised by Professor Adrian Hill and
Professor Brian Greenwood, CBE FRS,
the meeting is intended for researchers in
relevant fields and is free to attend, but preregistration online is essential.
For full details, visit http://www2.royalsociety.
org/events/forms/1010.htm
Next Vaccinology
Course at Oxford
This programme provides state-of-the-art
teaching in both veterinary and human
vaccinology, drawing on the experience of
Oxford University, through the Jenner Institute
based in Oxford, the Institute for Animal Health
(IAH) and our partners in industry to provide
training in areas related to vaccine design and
construction, including: immunology and
molecular biology, manufacturing, clinical trial
design, immunomonitoring, regulatory strategy,
post-marketing surveillance, vaccine financing
and the ethics of vaccination.
There are three courses currently
in the Vaccinology Programme:
Human and Veterinary
Vaccinology
29 November - 3 December 2010
(five-day course)
Clinical Vaccine Development
(two-day course)
Vaccine Biomanufacturing
(two-day course)
For more information visit
http://cpd.conted.ox.ac.uk/vaccinology
Bryan Charleston, Kruger National Park 2009
Decade of Vaccines - $10billion pledged by
the Bill and Melinda Gates Foundation
In Davos, Switzerland, at the World Economic
Forum in January this year, the Bill and
Melinda Gates Foundation announced the
unprecedented donation of $10billion to fund
a Decade of Vaccines. Urging the world’s donor
agencies, business concerns, governments
and non-profits to assist in this effort that will
dramatically reduce child mortality in the
world’s poorest countries, Bill Gates estimated
that 8 million lives could be saved by 2020.
For more on this topic
http://www.gatesfoundation.org/vaccines/
Pages/decade-of-vaccines.aspx
See next issue: “News of the efficacy
flu trials answering key questions”
Brian Greenwood CBE FRS (Chairman)
[email protected]
Jenner Vaccine Foundation
www.jennervaccinefoundation.org
12
ORCRB, Roosevelt Drive, Oxford OX3 7DQ
Clare Jeffrey (Development) +44 (0) 1865 617630
[email protected]
Gary Strickland (Administrator and Company Secretary)
+44 (0) 1865 617600
[email protected]